During our last funding period, we have helped the lithotripsy community recognize the severity of SWL adverse effects, and we have made a significant contribution to the understanding of the physical acoustic mechanisms of shock wave action involved in stone comminufion and tissue injury. However, from our perspective in this field we see there is still much that needs to be accomplished. In particular, the urology community is now faced with a new dilemma, in that lithotripsy is not getting better and the lithotripter itself has become a risk factor. Our multidisplanary team of scientist/clinicians is ideally situated to address these issues. The present renewal proposal has developed a plan of four interactive, collaborative projects to achieve the following goals. We will: 1. Identify and isolate factors that increase the risk of adverse effects in SWL. 2. Define the tissue response to SW's that leads to long-term renal damage. 3. Develop treatment strategies (protective mechanisms) that reduce the renal trauma suffered during lithotripsy. 4. Establish criteria for the selection of SW parameters (rate, voltage, number) for safe and effective SWL. 5. Evaluate the efficacy and safety of 3rd generation electromagnetic lithotripters, as a step toward determining how to improve SWL performed with these devices. 6. Develop real-time imaging and cavitation detection to allow the urologist to monitor tissue damage and stone comminution during SWL. 7. Test a new concept in SW delivery (dual pulse lithotripsy) for cavitation control to enhance stone breakage and minimize tissue injury. 8. Determine the mechanics of stone failure in SWL so that the lithotripter waveform can be perfected for efficient stone breakage. 9. Establish computational models that will simulate the critical features of shock wave action (the virtual lithotripter) and allow relevant predictions for systematic improvement of SWL. Our main goal is to improve shock wave lithotripsy - to make lithotripsy safer and more efficient for all patients.